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The cholecystokinin receptor antagonist L-364,718 reduces taurocholate-induced pancreatitis in rats.

AbstractCONCLUSION:
Our results suggest that the cholecystokinin (CCK) receptor antagonist L-364,718 has a protective effect on taurocholate-induced pancreatitis, and thus, it is inferred that CCK may have a significant pathophysiological role in the early phase of pancreatitis.
BACKGROUND:
Conflicting results have been obtained from studies designed to determine the role of CCK in the initial stages of pancreatitis.
METHODS:
We evaluated the protective effect of the CCK receptor antagonist L-364,718 (devazepide) and of the trypsin inhibitor camostat, on taurocholate-induced pancreatitis in rats. L-364,718 (1 mg/kg) or camostat (200 mg/kg) was administered intragastrically 30 min before the induction of pancreatitis.
RESULTS:
Infusion of sodium taurocholate (50 mg/kg) into the pancreaticobiliary duct caused severe pancreatitis with marked hyperamylasemia and reduction of tissue enzyme content at 12 h postinfusion. Pretreatment with L-364,718, but not with camostat, caused significant improvement in signs of experimental pancreatitis based on tissue enzyme content and morphology. Compared with untreated pancreatitis, there was relatively well-preserved lobular architecture, less edema, less infiltration of inflammatory cells, and more zymogen granules after L-364,718 pretreatment. Moreover, the reduction of enzyme content owing to pancreatitis was ameliorated by L-364,718 pretreatment.
AuthorsK H Kim, M G Lee, D G Kim
JournalInternational journal of pancreatology : official journal of the International Association of Pancreatology (Int J Pancreatol) Vol. 20 Issue 3 Pg. 205-11 (Dec 1996) ISSN: 0169-4197 [Print] United States
PMID9013282 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Benzodiazepinones
  • Cholagogues and Choleretics
  • Esters
  • Guanidines
  • Hormone Antagonists
  • Receptors, Cholecystokinin
  • Trypsin Inhibitors
  • camostat
  • Gabexate
  • Taurocholic Acid
  • Amylases
  • Devazepide
  • Sincalide
Topics
  • Amylases (blood)
  • Animals
  • Benzodiazepinones (pharmacology)
  • Cholagogues and Choleretics (pharmacology)
  • Devazepide
  • Esters
  • Gabexate (analogs & derivatives)
  • Guanidines (pharmacology)
  • Histocytochemistry
  • Hormone Antagonists (pharmacology)
  • Male
  • Pancreas (drug effects, pathology)
  • Pancreatitis (blood, chemically induced, pathology, prevention & control)
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cholecystokinin (antagonists & inhibitors)
  • Sincalide (antagonists & inhibitors)
  • Taurocholic Acid
  • Trypsin Inhibitors (pharmacology)

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